title: cAMP regulates ADP-induced HSP27 phosphorylation in human platelets.
abstract: Elevation of cAMP in platelets is recognized to play a suppressive role in platelet functions. We have previously shown that adenosine diphosphate (ADP)-induced phosphorylation of heat shock protein 27 (HSP27) via p38 mitogen-activated protein (MAP) kinase is correlated with platelet-derived growth factor (PDGF)-AB secretion and soluble CD40 ligand (sCD40L) release. In the present study, we investigated the relationship between cAMP and HSP27 phosphorylation in platelet function. 8-Bromoadenosine-3',5'-cyclic monophosphate (8-bromo-cAMP), a plasma membrane-permeable cAMP analogue, or cilostazol, an inhibitor of cAMP phosphodiesterase, markedly attenuated the ADP-induced phosphorylation levels of p38 MAP kinase. In addition, the ADP-induced HSP27 phosphorylation was suppressed by 8-bromo-cAMP or cilostazol. 8-Bromo-cAMP, forskolin and cilostazol remarkably reduced the ADP-stimulated PDGF-AB secretion and sCD40L release. These results strongly suggest that cAMP regulates ADP-stimulated platelet activation due to inhibition of HSP27 phosphorylation via p38 MAP kinase.
authors.affiliation: Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Enomoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Doi
authors.forename: Hideo
authors.initials: H
authors.lastname: Natsume
authors.forename: Kenji
authors.initials: K
authors.lastname: Kato
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D000077407:Cilostazol; D000242:Cyclic AMP / Q000097:blood*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; D010982:Platelet-Derived Growth Factor; D013777:Tetrazoles; C095477:platelet-derived growth factor AB; D023201:CD40 Ligand; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D048051:p38 Mitogen-Activated Protein Kinases; D000077407:Cilostazol